@article{RN6152,
   author = {Galvao, R. P. and Kasina, A. and McNeill, R. S. and Harbin, J. E. and Foreman, O. and Verhaak, R. G. and Nishiyama, A. and Miller, C. R. and Zong, H.},
   title = {Transformation of quiescent adult oligodendrocyte precursor cells into malignant glioma through a multistep reactivation process},
   journal = {Proc Natl Acad Sci U S A},
   volume = {111},
   number = {40},
   pages = {E4214-23},
   note = {1091-6490
Galvao, Rui Pedro
Kasina, Anita
McNeill, Robert S
Harbin, Jordan E
Foreman, Oded
Verhaak, Roel G W
Nishiyama, Akiko
Miller, C Ryan
Zong, Hui
P30 NS045892/NS/NINDS NIH HHS/United States
R01 CA136495/CA/NCI NIH HHS/United States
R01 NS074870/NS/NINDS NIH HHS/United States
R01-CA136495/CA/NCI NIH HHS/United States
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
United States
2014/09/24
Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):E4214-23. doi: 10.1073/pnas.1414389111. Epub 2014 Sep 22.},
   abstract = {How malignant gliomas arise in a mature brain remains a mystery, hindering the development of preventive and therapeutic interventions. We previously showed that oligodendrocyte precursor cells (OPCs) can be transformed into glioma when mutations are introduced perinatally. However, adult OPCs rarely proliferate compared with their perinatal counterparts. Whether these relatively quiescent cells have the potential to transform is unknown, which is a critical question considering the late onset of human glioma. Additionally, the premalignant events taking place between initial mutation and a fully developed tumor mass are particularly poorly understood in glioma. Here we used a temporally controllable Cre transgene to delete p53 and NF1 specifically in adult OPCs and demonstrated that these cells consistently give rise to malignant gliomas. To investigate the transforming process of quiescent adult OPCs, we then tracked these cells throughout the premalignant phase, which revealed a dynamic multistep transformation, starting with rapid but transient hyperproliferative reactivation, followed by a long period of dormancy, and then final malignant transformation. Using pharmacological approaches, we discovered that mammalian target of rapamycin signaling is critical for both the initial OPC reactivation step and late-stage tumor cell proliferation and thus might be a potential target for both glioma prevention and treatment. In summary, our results firmly establish the transforming potential of adult OPCs and reveal an actionable multiphasic reactivation process that turns slowly dividing OPCs into malignant gliomas.},
   keywords = {Animals
Antineoplastic Agents/pharmacology
Blotting, Western
Brain Neoplasms/genetics/*metabolism/pathology
Cell Cycle/drug effects/genetics
Cell Differentiation/drug effects/genetics
Cell Proliferation/drug effects/genetics
Cell Transformation, Neoplastic/genetics/*metabolism
Gene Expression Profiling
Glioma/genetics/*metabolism/pathology
Immunohistochemistry
Mice, Inbred NOD
Mice, Knockout
Mice, SCID
Mice, Transgenic
Neural Stem Cells/cytology/*metabolism
Neurofibromin 1/genetics/metabolism
Oligodendroglia/cytology/*metabolism
Oligonucleotide Array Sequence Analysis
Sirolimus/analogs & derivatives/pharmacology
Tamoxifen/pharmacology
Tumor Cells, Cultured
Tumor Suppressor Protein p53/genetics/metabolism
cancer
cellular quiescence
cellular reactivation
mTOR signaling},
   ISSN = {0027-8424 (Print)
0027-8424},
   DOI = {10.1073/pnas.1414389111},
   year = {2014},
   type = {Journal Article}
}

{"_id":"Rnoy5fziSANGZnzvH","bibbaseid":"galvao-kasina-mcneill-harbin-foreman-verhaak-nishiyama-miller-etal-transformationofquiescentadultoligodendrocyteprecursorcellsintomalignantgliomathroughamultistepreactivationprocess-2014","authorIDs":["5dce3b23dcea22df0100007c","5dec52fce16431f2010000c9","5dec5944e16431f2010000fa","5e0a5e7ace3ebce40100010e","5e2ff5be5bfc8ede0100003b","c8zrScQz6casKGL4t"],"author_short":["Galvao, R. P.","Kasina, A.","McNeill, R. S.","Harbin, J. E.","Foreman, O.","Verhaak, R. G.","Nishiyama, A.","Miller, C. R.","Zong, H."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Galvao"],"firstnames":["R.","P."],"suffixes":[]},{"propositions":[],"lastnames":["Kasina"],"firstnames":["A."],"suffixes":[]},{"propositions":[],"lastnames":["McNeill"],"firstnames":["R.","S."],"suffixes":[]},{"propositions":[],"lastnames":["Harbin"],"firstnames":["J.","E."],"suffixes":[]},{"propositions":[],"lastnames":["Foreman"],"firstnames":["O."],"suffixes":[]},{"propositions":[],"lastnames":["Verhaak"],"firstnames":["R.","G."],"suffixes":[]},{"propositions":[],"lastnames":["Nishiyama"],"firstnames":["A."],"suffixes":[]},{"propositions":[],"lastnames":["Miller"],"firstnames":["C.","R."],"suffixes":[]},{"propositions":[],"lastnames":["Zong"],"firstnames":["H."],"suffixes":[]}],"title":"Transformation of quiescent adult oligodendrocyte precursor cells into malignant glioma through a multistep reactivation process","journal":"Proc Natl Acad Sci U S A","volume":"111","number":"40","pages":"E4214-23","note":"1091-6490 Galvao, Rui Pedro Kasina, Anita McNeill, Robert S Harbin, Jordan E Foreman, Oded Verhaak, Roel G W Nishiyama, Akiko Miller, C Ryan Zong, Hui P30 NS045892/NS/NINDS NIH HHS/United States R01 CA136495/CA/NCI NIH HHS/United States R01 NS074870/NS/NINDS NIH HHS/United States R01-CA136495/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States 2014/09/24 Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):E4214-23. doi: 10.1073/pnas.1414389111. Epub 2014 Sep 22.","abstract":"How malignant gliomas arise in a mature brain remains a mystery, hindering the development of preventive and therapeutic interventions. We previously showed that oligodendrocyte precursor cells (OPCs) can be transformed into glioma when mutations are introduced perinatally. However, adult OPCs rarely proliferate compared with their perinatal counterparts. Whether these relatively quiescent cells have the potential to transform is unknown, which is a critical question considering the late onset of human glioma. Additionally, the premalignant events taking place between initial mutation and a fully developed tumor mass are particularly poorly understood in glioma. Here we used a temporally controllable Cre transgene to delete p53 and NF1 specifically in adult OPCs and demonstrated that these cells consistently give rise to malignant gliomas. To investigate the transforming process of quiescent adult OPCs, we then tracked these cells throughout the premalignant phase, which revealed a dynamic multistep transformation, starting with rapid but transient hyperproliferative reactivation, followed by a long period of dormancy, and then final malignant transformation. Using pharmacological approaches, we discovered that mammalian target of rapamycin signaling is critical for both the initial OPC reactivation step and late-stage tumor cell proliferation and thus might be a potential target for both glioma prevention and treatment. In summary, our results firmly establish the transforming potential of adult OPCs and reveal an actionable multiphasic reactivation process that turns slowly dividing OPCs into malignant gliomas.","keywords":"Animals Antineoplastic Agents/pharmacology Blotting, Western Brain Neoplasms/genetics/*metabolism/pathology Cell Cycle/drug effects/genetics Cell Differentiation/drug effects/genetics Cell Proliferation/drug effects/genetics Cell Transformation, Neoplastic/genetics/*metabolism Gene Expression Profiling Glioma/genetics/*metabolism/pathology Immunohistochemistry Mice, Inbred NOD Mice, Knockout Mice, SCID Mice, Transgenic Neural Stem Cells/cytology/*metabolism Neurofibromin 1/genetics/metabolism Oligodendroglia/cytology/*metabolism Oligonucleotide Array Sequence Analysis Sirolimus/analogs & derivatives/pharmacology Tamoxifen/pharmacology Tumor Cells, Cultured Tumor Suppressor Protein p53/genetics/metabolism cancer cellular quiescence cellular reactivation mTOR signaling","issn":"0027-8424 (Print) 0027-8424","doi":"10.1073/pnas.1414389111","year":"2014","bibtex":"@article{RN6152,\n author = {Galvao, R. P. and Kasina, A. and McNeill, R. S. and Harbin, J. E. and Foreman, O. and Verhaak, R. G. and Nishiyama, A. and Miller, C. R. and Zong, H.},\n title = {Transformation of quiescent adult oligodendrocyte precursor cells into malignant glioma through a multistep reactivation process},\n journal = {Proc Natl Acad Sci U S A},\n volume = {111},\n number = {40},\n pages = {E4214-23},\n note = {1091-6490\nGalvao, Rui Pedro\nKasina, Anita\nMcNeill, Robert S\nHarbin, Jordan E\nForeman, Oded\nVerhaak, Roel G W\nNishiyama, Akiko\nMiller, C Ryan\nZong, Hui\nP30 NS045892/NS/NINDS NIH HHS/United States\nR01 CA136495/CA/NCI NIH HHS/United States\nR01 NS074870/NS/NINDS NIH HHS/United States\nR01-CA136495/CA/NCI NIH HHS/United States\nJournal Article\nResearch Support, N.I.H., Extramural\nResearch Support, Non-U.S. Gov't\nUnited States\n2014/09/24\nProc Natl Acad Sci U S A. 2014 Oct 7;111(40):E4214-23. doi: 10.1073/pnas.1414389111. 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To investigate the transforming process of quiescent adult OPCs, we then tracked these cells throughout the premalignant phase, which revealed a dynamic multistep transformation, starting with rapid but transient hyperproliferative reactivation, followed by a long period of dormancy, and then final malignant transformation. Using pharmacological approaches, we discovered that mammalian target of rapamycin signaling is critical for both the initial OPC reactivation step and late-stage tumor cell proliferation and thus might be a potential target for both glioma prevention and treatment. In summary, our results firmly establish the transforming potential of adult OPCs and reveal an actionable multiphasic reactivation process that turns slowly dividing OPCs into malignant gliomas.},\n keywords = {Animals\nAntineoplastic Agents/pharmacology\nBlotting, Western\nBrain Neoplasms/genetics/*metabolism/pathology\nCell Cycle/drug effects/genetics\nCell Differentiation/drug effects/genetics\nCell Proliferation/drug effects/genetics\nCell Transformation, Neoplastic/genetics/*metabolism\nGene Expression Profiling\nGlioma/genetics/*metabolism/pathology\nImmunohistochemistry\nMice, Inbred NOD\nMice, Knockout\nMice, SCID\nMice, Transgenic\nNeural Stem Cells/cytology/*metabolism\nNeurofibromin 1/genetics/metabolism\nOligodendroglia/cytology/*metabolism\nOligonucleotide Array Sequence Analysis\nSirolimus/analogs & derivatives/pharmacology\nTamoxifen/pharmacology\nTumor Cells, Cultured\nTumor Suppressor Protein p53/genetics/metabolism\ncancer\ncellular quiescence\ncellular reactivation\nmTOR signaling},\n ISSN = {0027-8424 (Print)\n0027-8424},\n DOI = {10.1073/pnas.1414389111},\n year = {2014},\n type = {Journal Article}\n}\n\n","author_short":["Galvao, R. 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